tbuckley/cabot-search huggingface dataset:
Selected Articles from This Issue
Journal: Clinical Cancer Research (2023)

Highlights| November 14 2023 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2023 American Association for Cancer Research2023American Association for Cancer Research Clin Cancer Res (2023) 29 (22): 4519. https://doi.org/10.1158/1078-0432.CCR-29-22-HI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 14 2023 Citation Selected Articles from This Issue. Clin Cancer Res 15 November 2023; 29 (22): 4519. https://doi.org/10.1158/1078-0432.CCR-29-22-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search VEGFR is widely expressed in adenoid cystic carcinoma (ACC). In an open-label, multicenter, phase II clinical trial, Hanna and colleagues demonstrate antitumor activity with rivoceranib, a selective VEGFR-2 tyrosine kinase inhibitor, in patients with recurrent or metastatic ACC who had objective radiographic progression in the preceding 6 months, particularly among VEGFR-naïve patients. Antitumor activity was accompanied by a manageable safety profile consistent with other agents in this class. These findings suggest that selective inhibition of VEGFR-2 represents a potential treatment for ACC warranting further investigation. Patients with advanced/recurrent endometrial cancer have poor prognoses and limited treatment options following disease progression on frontline therapies. Deficient mismatch repair (dMMR) is a predictive biomarker for response to immune checkpoint inhibitors in endometrial cancer. In this interim analysis of the phase I GARNET trial, Oaknin and colleagues report that patients with advanced/recurrent endometrial cancer who had progressed on or after platinum therapy demonstrated durable... You do not currently have access to this content.
Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition
Authors: Haruka Wada, Ryo Otsuka, Wilfred T V Germeraad, Tomoki Murata, Toru Kondo, Ken-ichiro Seino
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background The cancer stem cell theory proposes that tumor formation in vivo is driven only by specific tumor-initiating cells having stemness; however, clinical trials conducted to test drugs that target the tumor stemness provided unsatisfactory results thus far. Recent studies showed clear involvement of immunity in tumors; however, the requirements of tumor-initiation followed by stable growth in immunocompetent individuals remain largely unknown. Methods To clarify this, we used two similarly induced glioblastoma lines, 8B and 9G. They were both established by overexpression of an oncogenic H-RasL61 in p53-deficient neural stem cells. In immunocompromised animals in an orthotopic transplantation model using 1000 cells, both show tumor-forming potential. On the other hand, although in immunocompetent animals, 8B shows similar tumor-forming potential but that of 9G’s are very poor. This suggests that 8B cells are tumor-initiating cells in immunocompetent animals. Therefore, we hypothesized that the differences in the interaction properties of 8B and 9G with immune cells could be used to identify the factors responsible for its tumor forming potential in immunocompetent animals and performed analysis. Results Different from 9G, 8B cells induced senescence-like state of macrophages around tumors. We investigated the senescence-inducing factor of macrophages by 8B cells and found that it was interleukin 6. Such senescence-like macrophages produced Arginase-1, an immunosuppressive molecule known to contribute to T-cell hyporesponsiveness. The senescence-like macrophages highly expressed CD38, a nicotinamide adenine dinucleotide (NAD) glycohydrolase associated with NAD shortage in senescent cells. The addition of nicotinamide mononucleotide (NMN), an NAD precursor, in vitro inhibited to the induction of macrophage senescence-like phenotype and inhibited Arginase-1 expression resulting in retaining T-cell function. Moreover, exogenous in vivo administration of NMN after tumor inoculation inhibited tumor-initiation followed by stable growth in the immunocompetent mouse tumor model. Conclusions We identified one of the requirements for tumor-initiating cells in immunocompetent animals. In addition, we have shown that tumor growth can be inhibited by externally administered NMN against macrophage senescence-like state that occurs in the very early stages of tumor-initiating cell development. This therapy targeting the immunosuppressive environment formed by macrophage senescence-like state is expected to be a novel promising cancer therapeutic strategy.
Implementing implementation science in global health
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2023)

The Lancet Global Health has just celebrated its 10-year anniversary. In this time, the journal has strived to promote the wellbeing of people in low-income and middle-income countries and of vulnerable populations worldwide by disseminating rigorous evidence to improve health equity. Nonetheless, a research-to-practice gap persists in global health. Implementation science is tasked with bridging this gap, transforming evidence into contextually appropriate practices. A focus on implementation in global health not only adds momentum towards real-world health impact, but it also empowers stakeholders in the communities of study and it encourages interdisciplinary and intersectional collaboration.
Converging global health agendas and universal health coverage: financing whole-of-government action through UHC+
Authors: Téa E Collins, Svetlana Akselrod, Rifat Atun, Sara Bennett, Osondu Ogbuoji, Mark Hanson, Grace Dubois, Ani Shakarishvili, Ilze Kalnina, Jennifer Requejo, Andrei Mosneaga, Akihito Watabe, Daria Berlina, Luke N Allen
Journal: The Lancet Global Health (2023)

UN member states have committed to universal health coverage (UHC) to ensure all individuals and communities receive the health services they need without suffering financial hardship. Although the pursuit of UHC should unify disparate global health challenges, it is too commonly seen as another standalone initiative with a singular focus on the health sector. Despite constituting the cornerstone of the health-related Sustainable Development Goals, UHC-related commitments, actions, and metrics do not engage with the major drivers and determinants of health, such as poverty, gender inequality, discriminatory laws and policies, environment, housing, education, sanitation, and employment. Given that all countries already face multiple competing health priorities, the global UHC agenda should be used to reconcile, rationalise, prioritise, and integrate investments and multisectoral actions that influence health. In this paper, we call for greater coordination and coherence using a UHC+ lens to suggest new approaches to funding that can extend beyond biomedical health services to include the cross-cutting determinants of health. The proposed intersectoral co-financing mechanisms aim to support the advancement of health for all, regardless of countries' income.
Innovations in genomic antimicrobial resistance surveillance
Authors: Nicole E Wheeler, Vivien Price, Edward Cunningham-Oakes, Kara K Tsang, Jamie G Nunn, Janet T Midega, Muna F Anjum, Matthew J Wade, Nicholas A Feasey, Sharon J Peacock, Elita Jauneikaite, Kate S Baker
Journal: The Lancet Microbe (2023)

Whole-genome sequencing of antimicrobial-resistant pathogens is increasingly being used for antimicrobial resistance (AMR) surveillance, particularly in high-income countries. Innovations in genome sequencing and analysis technologies promise to revolutionise AMR surveillance and epidemiology; however, routine adoption of these technologies is challenging, particularly in low-income and middle-income countries. As part of a wider series of workshops and online consultations, a group of experts in AMR pathogen genomics and computational tool development conducted a situational analysis, identifying the following under-used innovations in genomic AMR surveillance: clinical metagenomics, environmental metagenomics, gene or plasmid tracking, and machine learning. The group recommended developing cost-effective use cases for each approach and mapping data outputs to clinical outcomes of interest to justify additional investment in capacity, training, and staff required to implement these technologies. Harmonisation and standardisation of methods, and the creation of equitable data sharing and governance frameworks, will facilitate successful implementation of these innovations.
The future of cancer care in the UK—time for a radical and sustainable National Cancer Plan
Authors: Ajay Aggarwal, Ananya Choudhury, Nicola Fearnhead, Pam Kearns, Anna Kirby, Mark Lawler, Sarah Quinlan, Carlo Palmieri, Tom Roques, Richard Simcock, Fiona M Walter, Pat Price, Richard Sullivan
Journal: The Lancet Oncology (2023)
Tuberculosis and undernutrition in India
Authors: Sapna Negi, Snehasish Tripathy
Journal: The Lancet Global Health (2023)

One of the key finding of the RATIONS trial substudy1 is a significant association between weight gain and improved treatment outcomes. The study showed that a 5% weight gain was associated with a 61% decreased likelihood of tuberculosis mortality, particularly in the initial 2 months of treatment. This resonates with the findings of previous studies2 emphasising that nutritional intervention can help improve tuberculosis cure rate. Furthermore, the median 4·6 kg weight gain in the participants supports the efficacy of nutritional support.
People who inject drugs: testing and treatment of HIV and HCV
Authors: Md Safiullah Sarker
Journal: The Lancet Global Health (2023)

Globally, an estimated 15% of people who inject drugs are living with HIV, and 53% are living with hepatitis C virus (HCV).1 People who inject drugs are disproportionately affected by these infections and are at a high risk of acquiring and transmitting them. In December 2020, UNAIDS introduced bold new goals: for 95% of all people with HIV to be aware of their status, 95% of those diagnosed with HIV to be on continuous antiretroviral treatment, and 95% of those treated to have controlled viral loads by 2025.
Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group
Authors: Kate S Baker, Elita Jauneikaite, Jamie G Nunn, Janet T Midega, Rifat Atun, Kathryn E Holt, Kamini Walia, Benjamin P Howden, Heather Tate, Iruka N Okeke, Alessandra Carattoli, Li Yang Hsu, Katie L Hopkins, Dishon M Muloi, Nicole E Wheeler, David M Aanensen, Lewis C E Mason, Jonah Rodgus, Rene S Hendriksen, Sabiha Y Essack, Beverly Egyir, Alison L Halpin, Duncan R MacCannell, Josefina Campos, Padmini Srikantiah, Nicholas A Feasey, Sharon J Peacock
Journal: The Lancet Microbe (2023)

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.
Mental and physical health changes around transitions into unpaid caregiving in the UK: a longitudinal, propensity score analysis
Authors: Rebecca E Lacey, Baowen Xue, Giorgio Di Gessa, Wentian Lu, Anne McMunn
Journal: The Lancet Public Health (2023)

BackgroundThe health of unpaid caregivers is poorer, on average, than in non-caregivers. There has been little focus on how health changes when becoming a caregiver and whether this varies by age, gender, and caregiving intensity. We aimed to investigate the mental and physical health changes involved with becoming a caregiver and whether these associations varied by gender, caregiving intensity, or age.MethodsThis study used data from the UK Household Longitudinal Study (2009–20) to examine mental and physical health changes around the transition to becoming a caregiver in adults aged 16 years and older. We included adults with information on care, complete covariates needed for matching, and at least one measure of health before or after becoming a caregiver (or matched non-caregiver). Health was measured via General Health Questionnaire-12 (GHQ-12, psychological distress) and 12-item Short Form Survey (SF-12, physical and mental functioning). We applied piecewise growth curve modelling with propensity score matching to model trajectories of mental and physical health for caregivers and matched non-caregivers. Analyses were stratified by age group, gender, and caregiving intensity.FindingsSample sizes varied from 3025 (GHQ-12 analyses in early adulthood) to 5785 (SF-12 analyses in early mid-adulthood). Psychological distress increased during transition to caregiving for all ages, particularly in those younger than 64 years, those providing care for 20 h or more per week, and for someone living within the household. Mental health functioning worsened during caregiving transition for those aged 30–64 years, those providing 20 h or more per week, and for those caring for someone within the household. Physical health functioning did not change but there was evidence of lower levels of functioning before caregiving. Changes in mental and physical health upon transition to caregiving did not differ by gender.InterpretationOur findings highlight the importance of early identification of and support for caregivers, including younger caregivers. This is important to break the cycle of caregiving and future care need. Health services staff, including general practitioners and hospital discharge teams, are well positioned for early identification of caregivers. We also encourage particular support for the mental health of caregivers and particularly those who become caregivers at a younger age.FundingThe UK Economic and Social Research Council.
Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities
Authors: Elita Jauneikaite, Kate S Baker, Jamie G Nunn, Janet T Midega, Li Yang Hsu, Shweta R Singh, Alison L Halpin, Katie L Hopkins, James R Price, Padmini Srikantiah, Beverly Egyir, Iruka N Okeke, Kathryn E Holt, Sharon J Peacock, Nicholas A Feasey
Journal: The Lancet Microbe (2023)

Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in health-care facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the identified challenges and potential benefits of genomic AMR surveillance in health-care settings, and outline the recommendations of the working group to realise this potential. These recommendations include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics), and building capacity at local, national, and regional levels using hub and spoke models.
Genomics for public health and international surveillance of antimicrobial resistance
Authors: Kate S Baker, Elita Jauneikaite, Katie L Hopkins, Stephanie W Lo, Leonor Sánchez-Busó, Maria Getino, Benjamin P Howden, Kathryn E Holt, Lillian A Musila, Rene S Hendriksen, Daniel G Amoako, David M Aanensen, Iruka N Okeke, Beverly Egyir, Jamie G Nunn, Janet T Midega, Nicholas A Feasey, Sharon J Peacock
Journal: The Lancet Microbe (2023)

Historically, epidemiological investigation and surveillance for bacterial antimicrobial resistance (AMR) has relied on low-resolution isolate-based phenotypic analyses undertaken at local and national reference laboratories. Genomic sequencing has the potential to provide a far more high-resolution picture of AMR evolution and transmission, and is already beginning to revolutionise how public health surveillance networks monitor and tackle bacterial AMR. However, the routine integration of genomics in surveillance pipelines still has considerable barriers to overcome. In 2022, a workshop series and online consultation brought together international experts in AMR and pathogen genomics to assess the status of genomic applications for AMR surveillance in a range of settings. Here we focus on discussions around the use of genomics for public health and international AMR surveillance, noting the potential advantages of, and barriers to, implementation, and proposing recommendations from the working group to help to drive the adoption of genomics in public health AMR surveillance. These recommendations include the need to build capacity for genome sequencing and analysis, harmonising and standardising surveillance systems, developing equitable data sharing and governance frameworks, and strengthening interactions and relationships among stakeholders at multiple levels.
Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces
Authors: Dishon M Muloi, Elita Jauneikaite, Muna F Anjum, Sabiha Y Essack, David A Singleton, Mitchelle R Kasudi, Matthew J Wade, Beverly Egyir, Jamie G Nunn, Janet T Midega, Sharon J Peacock, Nicholas A Feasey, Kate S Baker, Ruth N Zadoks
Journal: The Lancet Microbe (2023)

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low-income and middle-income countries. Evidence of directionality, risks to human and animal health, and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health interfaces.
Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019
Authors: Chuan-Ya Jiang, Ke Han, Fan Yang, Si-Yue Yin, Lei Zhang, Bing-Yu Liang, Tai-Bao Wang, Tao Jiang, Yue-Rong Chen, Tai-Yu Shi, Yu-Chen Liu, Shan-Wen Chen, Bu-Sheng Tong, Ye-Hai Liu, Hai-Feng Pan, Yan-Xun Han
Journal: Ageing Research Reviews (2023)

As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its changes in the next 20 years, decomposed the trend according to demographic factors and epidemiological changes, and quantified the cross-country healthy inequalities, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. In 2019, there were more than 140 million cases of hearing loss worldwide, a 93.89% increase from 70 million cases in 1990. The age-standardized rate (ASR) also increased with an estimated annual percentage change of 0.08% per year. Population growth and aging are the major drivers contributing to the changes, accounting for 60.83% and 35.35%. Of note, the contribution of aging varies showing a gradual increasing trend with sociodemographic index (SDI) elevating. Also notable, there were significant health inequalities across 204 countries and territories, with slope index of inequality rising over time. Projection of the global burden of hearing loss from 2020 to 2040 indicated progressive increases in both case number and ASR. These reflect the heavy disease burden of hearing loss that needed more targeted and efficient strategies in its prevention and management.
Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial
Authors: Rémy Nicolle, Jean-Baptiste Bachet, Alexandre Harlé, Juan Iovanna, Pascal Hammel, Vinciane Rebours, Anthony Turpin, Meher Ben Abdelghani, Alice Wei, Emmanuel Mitry, Anthony Lopez, James Biagi, Eric François, Pascal Artru, Aurélien Lambert, Daniel J. Renouf, Laure Monard, Marjorie Mauduit, Nelson Dusetti, Thierry Conroy, Jérome Cros
Journal: Journal of Clinical Oncology (2023)

GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population.